Cytokine mRNA expression in intestinal tissue of interleukin-2 deficient mice with bowel inflammation.
BACKGROUND
Mice deficient in interleukin-2 (IL-2) develop inflammatory bowel disease resembling ulcerative colitis in humans. Recent studies provided evidence that alpha beta T cells, particularly CD4 T cells, rather than B cells, are involved in the pathogenesis of bowel inflammation of IL-2 deficient mice.


OBJECTIVE
To analyse the pattern of expression of cytokine mRNA in intestinal tissue of normal and IL-2 deficient mice.


METHODS
Expression of beta-actin, IL-1 alpha, IL-1 beta, IL-6, IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta 1 (TGF-beta 1) mRNA was analysed in colon and small intestinal tissue of both IL-2 deficient (IL-2-/-) mice and normal (wild type) litter mates (IL-2+/+) at different ages by using qualitative, as well as semiquantitative, competitive reverse transcription polymerase chain reaction (RT-PCR). Results were correlated with the phase of progression of the disease, as determined by histology.


RESULTS
IL-2-/- mice had expressed low levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma mRNA in the colon by 1.5 weeks of age. In advance of the development of histologically and clinically detectable bowel inflammation, expression of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and IL-10, but not TGF-beta 1, mRNA increased in the colon of IL-2 deficient mice. In contrast, IL-2+/+ mice expressed TGF-beta 1 mRNA in colon tissue at 13 and 23 weeks of age, but not IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IL-10, or IFN-gamma mRNA. Levels of expression of cytokine mRNA in tissue from the small intestine were comparable in IL-2-/- and IL-2+/+ mice.


CONCLUSIONS
Bowel inflammation in IL-2 deficient mice is preceded by an increase in IL-1 alpha, IL-1 beta, TNF-alpha, and IFN-gamma mRNA expression in colon tissue. Low levels of TGF-beta 1, but high levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and IL-10 mRNA expression correlate with the manifestation of severe colitis, and suggest that T cells and macrophages are involved in bowel inflammation of IL-2 deficient mice.
Autenrieth
I B
IB
Max v. Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität, München, Germany.
Bucheler
N
N
Bohn
E
E
Heinze
G
G
Horak
I
I
D000199:Actins / Q000235:genetics; D000818:Animals; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000172:deficiency*; D015850:Interleukin-6 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000199:Actins; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma